家族性2型糖尿病遗传方式及血糖血脂代谢的研究

目的：探索家族性2型糖尿病的遗传方式及家族性2型糖尿病家系一级亲属正常糖耐量同胞的血糖血脂代谢变化。方法：按WHO1980标准，收集江苏苏南地区2型糖尿病多发家系99个，进行3代家族史和血统成员的调查研究。检查血糖、血脂、葡萄炉子耐量及胰岛C肽释放试验。在排除糖尿病和糖耐量减低（IGT）的前提下，选择先证者的正常糖耐量同胞为观察组（54例），同胞的正常配偶为对照组（56例），进行血糖务脂代谢分析。结果：先证者的同胞患病率为46.7%。同胞患病率是其配偶的6.6倍；而同胞及其配偶的IGT患病率均为11%左右。病系谱分析显示，至少双亲之一为糖尿病患者的家系达50.5%，先证者同胞患糖尿病者达1/2。与配偶组比较同胞的TG、LDL、水平升高，空胆血糖升高，而胰岛素、C肽水平无差异。结论：有家族史的2型糖尿病患者有明显的家族集性，其发病与遗传密切相关，其遗传方式不完全支持多基因遗传，而支持孟德尔的常染色体显性遗传。同胞在糖耐量正常的情况下血糖、血脂已开始变化，对该糖尿病高危人群应进行血糖血脂监测以利早期防治。     

家族性2型糖尿病162个家系调查研究

目的　建立可用于系统研究 2型糖尿病 (T2 DM )遗传和环境危险因素的高发家系人群 ,探索家族性 2型糖尿病的遗传方式。方法　已诊断有糖尿病家族史的糖尿病先证者 175个进行 3代家族史和血统成员的调查研究 ,全部非糖尿病患者采血做OGTT确认 ,排除 1型糖尿病、MODY型和线粒体遗传阳性家系 ,最终筛选出具有 2个或 2个以上 2型糖尿病患者的家系 162个 (共 898例 )。全部家系成员均检查血糖、血脂、胰岛素C肽释放试验。结果　有 2个T2 DM患者的家系 91个 ,占5 6 2 % ;有 3个T2 DM患者的家系 61个 ,占 3 7 7% ;2代均有T2 DM患者的家系有 15 1个 ;3代均有T2 DM患者的家系 11个。先证者一级亲属 3 69人 ,其中患 2型糖尿病病 2 61例 ,占一级亲属的 70 7% ;先证者的同胞 2 78例 (不包括先证者 )中 ,有 2型糖尿病患者 12 6例 ,占 45 3 % ,同胞患病率是其配偶的 6 1倍。在 162个家系中未观察到有统计学意义的母系效应 ,男女两性的患病率没有显著差异。结论　有家族史的 2型糖尿病患者有明显的家族聚集性 ,其发病与遗传密切相关 ;其遗传方式不完全支持多基本因遗传 ,似支持孟德尔常染色体显性遗传     

家族性2型糖尿病家系中正常同胞的血糖血脂代谢

目的:研究家族性2型糖尿病家系一级亲属正常同胞的血糖血脂代谢变化。方法:收集江苏苏南地区2型糖尿病多发家系136个。在排除糖尿病和糖耐量异常的前提下,选择先证者同胞为观察组(n=108),先证者同胞的配偶为对照组(n=92),进行血糖血脂代谢分析。结果:与对照组比较,观察组的三酰甘油犤(11.62±0.74)mmol/L犦、低密度脂蛋白胆固醇犤(3.23±1.39)mmol/L犦、空腹血糖犤(4.59±0.54)mmol/L犦和口服葡萄糖2h血糖犤(5.12±1.16)mmol/L犦升高,差异有显著性意义(t=2.644～2.971,P均0.05);而空腹及口服葡萄糖2h胰岛素犤(11.7±4.9),(37.7±23.7)mu/L犦和C肽水平犤(1.94±1.35),(5.23±3.27)μg/L犦无明显差异(t=0.261～1.254,P均>0.05)。结论:家族性2型糖尿病家系一级亲属在糖耐量正常的情况下血糖、血脂已开始变化,提示有胰岛素不敏感。对该糖尿病高危人群应进行监测及教育以利早期防治。     

家族性2型糖尿病家系中正常同胞的血糖血脂代谢

目的：研究家族性2型糖尿病家系一级亲属正常同胞的血糖血脂代谢变化。方法：收集江苏苏南地区2型糖尿病多发家系136个。在排除糖尿病和糖耐量异常的前提下，选择先证者同胞为观察组(n=108)，先证者同胞的配偶为对照组(n=92)，进行血糖血脂代谢分析。结果：与对照组比较，观察组的三酰甘油[(11.624-0.74)mmol／L]、低密度脂蛋白胆固醇[(3.234-1.39)mmol／L]、空腹血糖[(4.594-0.54)mmol／L]和口服葡萄糖2h血糖[(5.124-1.16)mmol／L]升高，差异有显著性意义(t=2.644～2.971，P均0.05)；而空腹及口服葡萄糖2h胰岛素[(11.7&;#177;4.9)，(37.74-23.7)mu／L]和C肽水平[(1.944-1.35)，(5.234-3.27)ug/L]无明显差异(t=0.261～1.254，P均&;gt;0.05)。结论：家族性2型糖尿病家系一级亲属在糖耐量正常的情况下血糖、血脂已开始变化，提示有胰岛素不敏感。对该糖尿病高危人群应进行监测及教育以利早期防治。     

2型糖尿病家系一级亲属代谢综合征危险因素的临床研究

目的分析2型糖尿病家系一级亲属同胞代谢综合征危险因素。方法收集61个2型糖尿病家系同胞一级亲属作为研究组(n=142),以同胞配偶中的无糖尿病家族史的一级亲属作为对照组(n=138)。测定体重指数、腰围、臀围、血压、空腹血糖、三酰甘油、高密度脂蛋白胆固醇,非糖尿病的同胞行75克葡萄糖耐量试验。结果2型糖尿病家系一级亲属同胞代谢综合征的患病率(33.09%)显著高于无糖尿病家系一级亲属同胞(11.59%),χ2=17.34,P<0.01。糖尿病、高血压、血脂紊乱、中心性肥胖及糖尿病阳性家族史与代谢综合征密切相关(均P<0.05)。结论代谢综合征具有遗传倾向;向心性肥胖、糖尿病、高血压、高三酰甘油血症、低高密度脂蛋白血症是代谢综合征的重要危险因素。     

2型糖尿病家系同胞一级亲属代谢异常分析

目的:研究2型糖尿病同胞一级亲属代谢异常的发生情况。方法:以406个2型糖尿病家系,选择同胞一级亲(不包括先证者)作为研究组(n=800),先证者及其同胞配偶(除外有糖尿病家族史者)作为配偶(群体对照)组(n=514),共采样1314个个体。比较两组间体质量指数,空腹及餐后2h血糖,空腹血三酰甘油及高密度脂蛋白胆固醇,血压,空腹及餐后2h血胰岛素,空腹及餐后2h血C肽,以及作两组间代谢异常的发生率的比较。结果:同胞组与配偶组间在空腹血糖犤(4.79±0.82)和(4.55±0.72)mmol/L,P=0.0001犦,高密度脂蛋白-胆固醇犤(1.20±0.38)和(1.26±0.42)mmol/L,P=0.02犦,收缩压犤(120±18)和(123±20)mmHg,1mmHg=0.133kPa,P=0.01犦这些参数之间差异均有显著性意义。在代谢异常的发生率的比较中,同胞组比配偶组显示出更高的代谢异常发生率,除单高血压外其余不论为单个代谢紊乱(单糖尿病,单血脂紊乱)还是两项代谢紊乱(糖尿病+高血压,糖尿病+血脂紊乱,高血压+血脂紊乱)或典型代谢综合征在同胞组的发生率均较配偶组发生率明显增高(χ2=1.33～114.08,P<0.05)。结论:2型糖尿病同胞一级亲比群体对照组表现出更多的代谢异常。有必要进行包括糖尿病在内的各项代谢指标的早期预防性干预。     

2型糖尿病家系非糖尿病一级亲属胰岛素抵抗的多因素分析

目的:研究2型糖尿病家系非糖尿病一级亲属胰岛素抵抗和体质量指数、血脂、血糖、胰岛素、C肽等参数的关系。方法:在重庆地区选择有两个或两个以上2型糖尿病患者的103个家系进行调查。对先证者的父母、同胞、和子代进行标准口服葡萄糖耐量实验,根据糖耐量结果确定无糖尿病者125例为一级亲属组。选择糖尿病患者或糖尿病家系一级亲属的配偶83例为正常对照组。比较两组空腹血糖、空腹胰岛素、空腹C肽、血脂,及糖负荷后60,120,180min血糖、胰岛素、C肽水平,并计算体质量指数及胰岛素抵抗稳态模型评估胰岛素抵抗指数(HOMA-IR),用于评价胰岛素抵抗变化。将一级亲属组成员根据体质量指数分组。比较肥胖者(n=57)和非肥胖者(n=68)的指标改变。结果:一级亲属组收缩压、舒张压、三酰甘油、总胆固醇、低密度脂蛋白胆固醇、HOMA-IR明显高于正常对照组(t=1.98～2.50,P<0.05～0.01)。葡萄糖负荷后60,120min的血糖及0,60min,120min的胰岛素,负荷后60min的C肽,均显著高于对照组(t=2.07～4.82,P<0.05～0.01)。一级亲属组肥胖者的三酰甘油,高密度脂蛋白胆固醇、低密度脂蛋白胆固醇空腹胰岛素水平及HOMA-IR明显高于非肥胖者t=2.03～7.56,P<0.05～0.01)。糖尿病一级亲属组HOMA-IR(与体质量指数,收缩压、舒张压、三酰甘油呈显著     

2型糖尿病家系一级亲属脂代谢紊乱和胰岛素抵抗变化的研究

目的　探讨 2型糖尿病家系一级亲属非糖尿病同胞脂代谢紊乱和胰岛素抵抗的情况。方法　检测了 5 2例 2型糖尿病家系一级亲属非糖尿病同胞 (FDR)和 19例正常对照组的体重指数、腰围、臀围、腰臀比、血压、血糖、血脂和胰岛素水平。采用稳态模式 (HOMA IR)评价胰岛素抵抗。结果　FDR组的腰围 (W )、臀围 (H)、体重指数(BMI)、空腹胰岛素 (FINS)和HOMA IR明显高于对照组 (P <0 .0 1)。多元逐步回归分析显示 ,空腹血糖 (FBG)、BMI和家族史是影响 2型糖尿病家系一级亲属非糖尿病同胞胰岛素抵抗主要的危险因素。结论　 2型糖尿病家系一级亲属非糖尿病同胞在未发生糖尿病时已存在高胰岛素血症和胰岛素抵抗 ,并且可能与遗传有关     

2型糖尿病家系同胞一级亲属代谢异常分析

目的：研究2型糖尿病同胞一级亲属代谢异常的发生情况。方法：以406个2型糖尿病家系，选择同胞一级亲(不包括先证者)作为研究组(n=800)，先证者及其同胞配偶(除外有糖尿病家族史者)作为配偶(群体对照)组(n=514)，共采样1314个个体。比较两组间体质量指数，空腹及餐后2h血糖，空腹血三酰甘油及高密度脂蛋白胆固醇，血压．空腹及餐后2h血胰岛素，空腹及餐后2h血C肽，以及作两组间代谢异常的发生率的比较。结果：同胞组与配偶组间在空腹血糖[(4.79&;#177;0.82)和(4.55&;#177;0.72)mmol／L，P=0.0001]，高密度脂蛋白-胆固醇[(1.20&;#177;0.38)和(1.26&;#177;0.42)mmol／LP=0.02]，收缩压[(120&;#177;18)和(123&;#177;20)mmHg，1mmHg=0.133kPa，P=0.01]这些参数之间差异均有显著性意义。在代谢异常的发生率的比较中，同胞组比配偶组显示出更高的代谢异常发生率，除单高血压外其余不论为单个代谢紊乱(单糖尿病，单血脂紊乱)还是两项代谢紊乱(糖尿病+高血压，糖尿病+血脂紊乱，高血压+血脂紊乱)或典型代谢综合征在同胞组的发生率均较配偶组发生率明显增高(r=1.33～114.08，P&;lt;0.05)。结论：2型糖尿病同胞一级亲比群体对照组表现出更多的代谢异常。有必要进行包括糖尿病在内的各项代谢指标的早期预防性干预。     

2型糖尿病家系成员血压与胰岛素抵抗的关系

目的:探讨2型糖尿病家系成员血压与胰岛素抵抗的关系,为糖尿病的一级康复预防提供依据。方法:对2型糖尿病家系成员进行口服葡萄糖耐量试验(OGTT),按1997年美国糖尿病学会诊断标准将家系成员分成糖尿病一级亲属糖耐量正常(NGT)组(96例),糖耐量减低(IGT)组(46例)和新诊断糖尿病组(63例),检测其血压、血脂、血浆胰岛素,计算胰岛素敏感性指数(ISI),与无糖尿病家族史的健康人(57例)相比较。结果:家系各组成员收缩压、舒张压、三酰甘油水平均显著高于正常对照组,如NGT组收缩压(119±17)mmHg,IGT组为(128±18)mmHg,新诊断糖尿病组(129±20)mmHg,正常对照组(109±17)mmHg(P<0.05或P<0.01),ISI和高密度脂蛋白胆固醇(HDL-C)显著低于正常对照组,如ISI在NGT组为-3.80±0.39,在IGT组-4.17±0.50,新诊断糖尿病组-4.53±0.53,正常对照组-3.58±0.58。血压与ISI、HDL-c呈显著负相关关系,与三酰甘油、体质量指数呈显著正相关关系,在多种因素中,ISI对收缩压的影响程度最大。结论:2型糖尿病家系一级亲属在糖耐量正常时,血压均已开始升高,随着代偿性高胰岛素血症持续到IGT及糖尿病阶段,血压进一步升高,而ISI则持续降低。一级亲属的血压变化可能是家族性2型糖尿病的遗传标志之一。     

2型糖尿病家系一级亲属血清脂联素与胰岛素抵抗的关系及其临床意义

目的：探讨2型糖尿病（T2DM）家系正常糖耐量一级亲属（简称一级亲属）血清脂联素水平的变化。研究脂联素与胰岛素抵抗（IR）的关系及其临床意义。方法：收集T2DM家系45个。在排除糖尿痛和糖耐量减退的前提下，选择一级亲属为观察组（83例），先证者或其同胞的配偶为正常对照组（76例），检测所有受试者的空腹脂联素、血糖、胰岛素、胰岛素原、血脂水平。采用稳态模型法（HOMA）计算胰岛素抵抗指数（HOMA-IR）。结果：一级亲属组的脂联素显著低于正常对照组（P〈0．01），HOMA-IR显著高于正常对照组（P〈0．05）。相关分析显示脂联素与收缩压、舒张压、血糖、年龄、体重指数、HOMA-IR呈负相关（P〈0．05或P〈0．01）。多元线性逐步回归分析显示，脂联素是影响T2DM家系一级亲属IR的独立危险因素。结论：T2DM家系一级亲属在未发生糖尿病时已存在IR、低脂联素血症，脂联素可能影响T2DM家系一级亲属IR的程度。     

脂肪细胞因子水平与2型糖尿病家系一级亲属的相关性

目的探讨2型糖尿病(T2DM)家系糖耐量正常的一级亲属(一级亲属)血清脂肪细胞因子中抵抗素、瘦素、脂联素表达水平的变化。方法收集广西壮族T2DM家系45个,在排除DM和糖耐量损害的前提下,选择一级亲属为观察组(83例),先证者的配偶或其同胞的配偶为健康对照组(76例),检测所有受试者的空腹血糖(FPG)、胰岛素(FIns)、胰岛素原(FPI)、血脂、抵抗素、瘦素、脂联素等。结果一级亲属组的抵抗素、瘦素、三酰甘油(TG)、FPI、FIns水平显著高于健康对照组(P<0.05或P<0.01),脂联素、高密度脂蛋白(HDL)显著低于健康对照组(P<0.05)。结论T2DM家系一级亲属存在高抵抗素、高瘦素血症,低脂联素血症。     

Familial clustering of arterial blood pressure, HDL cholesterol, and pro-insulin but not of insulin resistance and microalbuminuria in siblings of patients with type 2 diabetes

OBJECTIVE: To test the hypothesis that selected abnormalities cluster in type 2 diabetic families. Offspring of patients with type 2 diabetes have a 40-60% chance of developing type 2 diabetes and an increased frequency of impaired glucose tolerance (IGT) or unknown diabetes. These offspring also show metabolic abnormalities of type 2 diabetes, such as insulin resistance, high insulin and pro-insulin, low HDL cholesterol levels, arterial hypertension, and microalbuminuria. RESEARCH DESIGN AND METHODS: We studied 87 families including at least one type 2 diabetic patient, i.e., 87 probands and 146 siblings; 60 spouses of probands with no family history of diabetes were compared with siblings. Familial clustering was evaluated by 2 methods: concordance of siblings and probands for a given abnormality (method 1) and intraclass correlation coefficients of values within each family (method 2). RESULTS: At oral glucose tolerance testing, 24 siblings had type 2 diabetes, 31 siblings had IGT, and 14 spouses had IGT (P = 0.0012 vs. siblings). With method 1, familial clustering occurred for microalbuminuria, insulin resistance, arterial hypertension, HDL cholesterol and pro-insulin levels; with method 2, familial clustering was observed for the same variables except for microalbuminuria. With both method 1 and 2, familial clustering for insulin resistance disappeared, whereas familial clustering for arterial blood pressure, HDL cholesterol, and pro-insulin remained after correction for BMI; after further restriction of analysis to probands and to siblings with normal glucose tolerance, familial clustering for pro-insulin was observed only with method 2. CONCLUSIONS: These data indicate that siblings of diabetic patients are at high risk for selected features of type 2 diabetes.     

Insulin and C-peptide levels, pancreatic beta cell function, and insulin resistance across glucose tolerance status in Thais

Impaired pancreatic beta cell function and insulin sensitivity are fundamental factors in the pathogenesis of type 2 diabetes; however, the predominant defect appears differ among ethnic groups. We conducted a cross-sectional study to evaluate the contribution of impaired beta cell function and insulin sensitivity at different stages of the deterioration of glucose tolerance in Thais. The study involved 420 urban Thais of both sexes, 43-84 years old. A 75-g oral glucose tolerance test was performed on all of the subjects. Indices of insulin resistance and beta cell function were calculated with the use of a homeostasis model assessment. The subjects were classified as having normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined IFG and IGT, or type 2 diabetes mellitus according to the American Diabetes Association (ADA) criteria. There were no differences between groups with regard to gender and age. The percentage of obesity was significantly greatest in the diabetic group. Fasting serum insulin and C-peptide levels progressively increased from the NGT to the diabetic subjects. Serum C-peptide was more strongly associated with newly diagnosed diabetes than insulin, and was an independent factor associated with newly diagnosed diabetic subjects. The insulin resistance index progressively increased when the glucose tolerance stage changed from NGT through diabetic subjects. Beta cell function did not change significantly in any other group compared to the NGT group. An increase in fasting serum C-peptide may be a risk factor for type 2 diabetes. Obesity and insulin resistance are the predominant features in the deterioration of glucose tolerance in Thais.     

Diabetes in the Old Order Amish: characterization and heritability analysis of the Amish Family Diabetes Study

OBJECTIVE: The Old Order Amish (OOA) are a genetically well-defined closed Caucasian founder population. The Amish Family Diabetes Study was initiated to identify susceptibility genes for type 2 diabetes. This article describes the genetic epidemiology of type 2 diabetes and related traits in this unique population. RESEARCH DESIGN AND METHODS: The study cohort comprised Amish probands with diabetes who were diagnosed between 35 and 65 years of age and their extended adult family members. We recruited 953 adults who represented 45 multigenerational families. Phenotypic characterization included anthropometry, blood pressure, diabetes status, lipid profile, and leptin levels. RESULTS: The mean age of study participants was 46 years, and the mean BMI was 26.9 kg/m2. Subjects with type 2 diabetes were older, more obese, and had higher insulin levels. The prevalence of diabetes in the OOA was approximately half that of the Caucasian individuals who participated in the Third National Health and Nutrition Examination Survey (95% CI 0.23-0.84). The prevalence of diabetes in the siblings of the diabetic probands was 26.5% compared with a prevalence of 7.0% in spouses (lambdaS = 3.28, 95% CI 1.58-6.80). The heritability of diabetes-related quantitative traits was substantial (13-70% for obesity-related traits, 10-42% for glucose levels, and 11-24% for insulin levels during the oral glucose tolerance test; P = 0.01 to <0.0001). CONCLUSIONS: Type 2 diabetes in the Amish has similar phenotypic features to that of the overall Caucasian population, although the prevalence in the Amish community is lower than that of the Caucasian population. There is significant familial clustering of type 2 diabetes and related traits. This unique family collection will be an excellent resource for investigating the genetic underpinnings of type 2 diabetes.     

Reduced insulin secretion in offspring of African type 2 diabetic parents

OBJECTIVE: To determine the early biochemical predictors of increased susceptibility to develop diabetes in offspring of African type 2 diabetic parents. RESEARCH DESIGN AND METHODS: A total of 69 offspring (case subjects) of 26 families in Cameroon with at least one type 2 diabetic parent were studied, and 62 offspring (control subjects) from 25 families in Cameroon with no parent with type 2 diabetes underwent an oral glucose tolerance test. Early insulin secretion was calculated using the ratio of the 0- to 30-min incremental insulin values to the 0- to 30-min incremental glucose. Anthropometric parameters were also measured. RESULTS: Of the case subjects, 23% were glucose intolerant (4% with diabetes and 19% with impaired glucose tolerance [IGT]) compared with 6.5% (all with IGT) of control subjects (P = 0.02). There was also an increasing prevalence of glucose intolerance, especially IGT with increasing number of glucose-intolerant parents. Fasting serum insulin levels were not different in the two groups; however, at 30 min, the case subjects had lower insulin levels than the control subjects (P < 0.006). Case subjects with IGT had lower 30-min insulin concentration, early insulin secretion, and 2-h insulin levels than those with normal glucose tolerance (NGT) (F = 4.1, P < 0.05; F = 4.1, P < 0.04; and F = 5.1, P < 0.03, respectively). Furthermore, case subjects with NGT and IGT had lower early insulin secretion than control subjects (F = 4. 1, P < 0.03). These differences remained after adjustment for BMI and regardless of the status of parental diabetes. Two-hour insulin concentration showed a positive association (odds ratio = 0.95 CI 0.90-0.99, P = 0.039) with IGT in the case subjects. CONCLUSIONS: Diabetes and IGT are more prevalent in the offspring of African type 2 diabetic parents, and this may be due to an underlying degree of beta-cell impairment marked by reduced early-phase insulin secretion.     

Abnormal glucose tolerance and increased risk for cardiovascular disease in Japanese-Americans with normal fasting glucose

OBJECTIVE: To compare the American Diabetes Association (ADA) fasting glucose and the World Health Organization (WHO) oral glucose tolerance test (OGTT) criteria for diagnosing diabetes and detecting people at increased risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: Study subjects were 596 Japanese-Americans. Fasting insulin, lipids, and C-peptide levels; systolic and diastolic blood pressures (BPs); BMI (kg/m2); and total and intra-abdominal body fat distribution by computed tomography (CT) were measured. Study subjects were categorized by ADA criteria as having normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetic fasting glucose and by WHO criteria for a 75-g OGTT as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT). RESULTS: Of 503 patients with NFG, 176 had IGT and 20 had DGT These patients had worse CVD risk factors than those with NGT . The mean values for NGT, IGT, and DGT, respectively, and analysis of covariance P values, adjusted for age and sex, are as follows; intra-abdominal fat area by CT 69.7, 95.0, and 101.1 cm2 (P < 0.0001); total CT fat area 437.7, 523.3, and 489.8 cm2 (P < 0.0001); fasting triglycerides 1.40, 1.77, and 1.74 mmol/l (P = 0.002); fasting HDL cholesterol 1.56, 1.50, and 1.49 mmol/l (P = 0.02); C-peptide 0.80, 0.90, 0.95 nmol/l (P = 0.002); systolic BP 124.9, 132.4, and 136.9 mmHg (P = 0.0035); diastolic BP 74.8, 77.7, and 78.2 mmHg (P = 0.01). CONCLUSIONS: NFG patients who had IGT or DGT had more intra-abdominal fat and total adiposity; higher insulin, C-peptide, and triglyceride levels; lower HDL cholesterol levels; and higher BPs than those with NGT. Classification by fasting glucose misses many Japanese-Americans with abnormal glucose tolerance and less favorable cardiovascular risk profiles.     

Predictors of changes in glucose tolerance status in obese youth

OBJECTIVE: Type 2 diabetes in obese youth is an emerging problem. The metabolic and anthropometric predictors of change in glucose tolerance status in obese youth are unknown. RESEARCH DESIGN AND METHODS: A total of 117 obese children and adolescents were studied by performing an oral glucose tolerance test (OGTT) at baseline and after approximately 2 years. Data from both OGTTs and changes in weight were examined to identify youth at highest risk for developing diabetes and the factors that have the strongest impact on glucose tolerance. RESULTS: Eighty-four subjects had normal glucose tolerance (NGT) and 33 impaired glucose tolerance (IGT) at baseline. Eight subjects (all of whom had IGT at baseline) developed type 2 diabetes, whereas 15 subjects with IGT reverted to NGT. In this cohort, severe obesity, impaired glucose tolerance, and African-American background emerged as the best predictors of developing type 2 diabetes, whereas fasting glucose, insulin, and C-peptide were nonpredictive. Changes in insulin sensitivity, strongly related to weight change, had a significant impact on the 2-h glucose level on the follow-up study. CONCLUSIONS: Severely obese children and adolescents with IGT, particularly of African-American descent, are at very high risk for developing type 2 diabetes over a short period of time. Parameters derived from an OGTT and not fasting samples can serve as predictors of changes in glucose tolerance.     

The Singapore impaired glucose tolerance follow-up study: does the ticking clock go backward as well as forward?

OBJECTIVE: To 1). document the change in glucose tolerance for subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) over time, 2). identify baseline factors associated with worsening of glucose tolerance, and 3). determine whether cardiovascular disease (CVD) risk factors associated with IGT improved in tandem with glucose tolerance. RESEARCH DESIGN: Subjects with IGT and NGT (matched for age, sex, and ethnic group) were identified from a cross-sectional survey conducted in 1992. Subjects with IGT (297) and NGT (298) (65.0%) were reexamined in 2000. Glucose tolerance (assessed by 75-g oral glucose tolerance test), anthropometric data, serum lipids, blood pressure, and insulin resistance were determined at baseline and at the follow-up examination. RESULTS: For NGT subjects, 14.0% progressed to IGT and 4.3% to diabetes over 8 years. For IGT subjects, 41.4% reverted to NGT, 23.0% remained impaired glucose tolerant, and 35.1% developed diabetes. Obesity, hypertriglyceridemia, higher blood pressure, increased insulin resistance, and lower HDL cholesterol at baseline were associated with worsening of glucose tolerance in both IGT and NGT subjects. Those with IGT who reverted to NGT remained more obese and had higher blood pressure than those with NGT in both 1992 and 2000. However, serum triglyceride, HDL cholesterol, and insulin resistance values in 2000 became indistinguishable from those of subjects who maintained NGT throughout the study period. CONCLUSIONS: Some, but not all, CVD risk factors associated with IGT and with the risk of future diabetes normalize when glucose tolerance normalizes. Continued surveillance and treatment in subjects with IGT, even after they revert to NGT, may be important in the prevention of CVD.